Treating asthma, chronic obstructive pulmonary disease and/or other respiratory difficulties

ABSTRACT

A method of treatment and/or prophylaxis of a mammal for at least the symptoms of treating asthma, chronic obstructive pulmonary disease and/or other respiratory difficulties which comprises or includes administering or having self administered to such mammal an effective amount of either (a) cetyl myristate, or (b) cetyl myristate and cetyl palmitate.

TECHNICAL FIELD

The present invention relates to a method of treatment and/orprophylaxis of at least the symptoms of asthma, chronic obstructivepulmonary disease and/or other respiratory difficulties.

BACKGROUND

Asthma is a condition that affects your airways primarily the smalltubes that carry air in and out of the lungs. Those who suffer Asthmahave airways that are almost always red and sensitive. The rednessusually indicates that the airways are inflamed. There are variousAsthma triggers and can include things such as a cold or flu, exercise,allergies to things such as pollen, fur or dust mites. EssentiallyAsthma causes breathing problems, it can he life threatening and is adisease that affects the lungs. Chronic obstructive pulmonary disease isan extreme example of respiratory disease and currently is not known tohave a cure.

Asthma can have very damaging effects on a persons normal way of lifewhere they may no longer exercise or get out and about to enjoythemselves for fear of having an Asthma attack. To control this outsetof an Asthma attack people take various prescribed medication includingFLIXOTIDE™, RESPICORT™ etc or simply do not bring themselves into asituation in which an Asthma attack could be brought about.

The present invention has surprisingly determined that theadministration (particularly by ingestion) of cetyl myristate, andparticularly cetyl myristate in conjunction with cetyl palmitate,provides an effective treatment of at least the symptoms of asthma,chronic obstructive pulmonary disease and/or other respiratorydifficulties. This effect is experienced in as little as 2 weeks forthose patients suffering chronic obstructive pulmonary disease.

Cetyl myristate and cetyl palpitate can each be sourced from animals orvegetables. Cetyl myristate is not to be mistaken for cetyl myristoleatewhich is also a fatty acid derived traditionally from spermaceti bysaponification and more recently from the tallow of bovine(s).

Reference is made to U.S. Pat. No. 4,113,881 where it is disclosed thatthe administration of an effective amount of cetyl myristoleate to amammal is useful in inhibiting or relieving the symptoms of inflammatoryrheumatoid arthritis in mammals. Also in U.S. Pat. No. 5,569,676 thereis disclosure of the use of cetyl myristoleate in the treatment ofosteo-arthritis.

It is thought that cetyl myristate has a negligible anti-arthriticactivity in laboratory experiments and reference is made to the websitewww.gcinutrients.com/Newletter.com. However this point is arguable and aproduct known as cetyl myristate sold by Amerex Corporation of 770Sycamore Avenue, Suite J148, Vista, Calif. 92083, USA purports thatcetyl myristate is useful for the treatment of arthritis.

Cetyl myristate is derived from the saturated fatty acid, myristic acid.This acid is found in nutmeg butter, in the fats of Myristicaceae, inpalm seed fats, milk fats and also sperm whale oil. Reference is made toU.S. Pat. No. 2,481,365 which discloses the preparation of mystic acidfrom tall-oil fatty acids. It is to be noted that Amerex Corporationsource the cetyl myristate used in their products from sunflower oil.See their website at www.hollinet.com.

Cetyl palmitate is derived from the fatty acid, palmitic acid whichoccurs as the glycerol ester in many oils and fats such as palm oil orChinese vegetable tallow. A synthetic method of preparation is to reactpalmitoyl chloride and cetyl alcohol in the presence of magnesium. Seethe Merck Index, 12th edition at page 336. Reference is also made toU.S. Pat. No. 3,169,099 which discloses a biosynthetic method ofproducing cetyl palmitate.

It is an objection of the present invention to provide a medicament toaid in the treatment of asthma, chronic obstructive pulmonary diseaseand/or other respiratory difficulties which will provide an alternativeto existing treatments or to provide the public with a useful choice.

DISCLOSURE OF INVENTION

As indicated earlier the present invention is directed to the, treatmentand/or prophylaxis of at least the symptoms of asthma, chronicobstructive pulmonary disease and/or other respiratory difficultiesreliant upon administration (whether by self administration orotherwise) of either cetyl myristate or cetyl myristate and cetylpalmitate (whether given simultaneously in admixture or not or givenserially or co-administration).

The present invention also encompasses the prospect of dosage forms thatin some instances might contain cetyl myristate alone and in otherinstances both cetyl myristate and cetyl palmitate and dosage regimesthat might use one dosage form or both.

Without being bound to our theory we believe that the present inventionhas a beneficial effect on Mast cells by stabilising these cells. Mastcells have Immunoglobulin receptors on their surfaces and are known tomediate aspects of allergic and inflammatory reactions. See Renew ofMedical Physiology, by William F Garnong [15 ED].

It is believed that the stabilisation of these Mast cells prevents theallergic and inflammatory reaction occurring in the body that isresponsible for asthma, chronic obstructive pulmonary disease and/orother respiratory difficulties. It is also thought this theory isequally applicable to our other patent applications as described in ourNew Zealand Patent Application No's. 504524, 504525/507228, 504526 and502779, and also as described in our corresponding PCT Applications;PCT/NZ01/00084, PCT/NZ01/00085 and PCT/NZ01/00086.

STATEMENTS OF INVENTION

In a first aspect the invention is a method of treatment and/orprophylaxis of a mammal for at least the symptoms of treating asthma,chronic obstructive pulmonary disease and/or other respiratorydifficulties which comprises or includes administering or having selfadministered to such mammal an effective amount of either

-   -   (a) cetyl myristate, or    -   (b) cetyl myristate and cetyl palmitate.

Preferably and administration is orally of (b) whether as a mixture ofboth cetyl myristate and cetyl palmitate, or serially.

Preferably the effective amount is of (b).

Preferably said administration is with a mixture of cetyl myristate inconjunction with cetyl palmitate where the cetyl myristate comprisesfrom 50 to 98% w/w of the mixture.

Preferably said effective amount of (a) or (b) is by means of one ormore capsules.

The method also extends to related conditions, eg; accelerated woundhealing where a composition as disclosed in U.S. Pat. No. 4,775,291 canat least sometimes be supplemented by use of the present inventionmethodology.

In another aspect the invention is an oral pharmaceutical compositionfor treating asthma, chronic obstructive pulmonary disease and/or otherrespiratory difficulties which comprises or includes both cetylmyristate and cetyl palmitate.

Preferably said cetyl myristate comprises at least 50% w/w of thecomposition.

Preferably said composition also includes at least one pharmaceuticallyacceptable excipient and/or diluent.

In still another aspect the invention is an oral dosage unit effectivein the treatment of asthma, chronic obstructive pulmonary disease and/orother respiratory difficulties, said dosage unit having either

-   -   (a) cetyl myristate, or    -   (b) a mixture of cetyl myristate and cetyl palmitate.

Preferably said dosage unit is (b) and said cetyl myristate in any suchmixture comprises from 50 to 98% w/w of the mixture.

In another variant the dosage unit has (a) only and there is between 5to 400 mg of cetyl myristate.

Preferably in the dosage use, where (b) is present, there is from 5 to400 mg of the mixture of cetyl myristate and cetyl palmitate.

Preferably (a) or (b) is in a capsule.

Preferably said capsule also includes a pharmaceutically acceptableexcipient and/or diluent.

Preferably the dosage unit includes silicon dioxide.

Preferably the dosage unit also contains calcium phosphate and/ormagnesium oxide.

Preferably the dosage unit also includes additionally at least one traceelement.

In another aspect the invention is a liquid dosage unit being also anoral dosage unit as aforesaid.

In another aspect the invention is tile use, in the manufacture of oraldosage units for the treatment or prophylaxis of at least the symptomsof asthma, chronic obstructive pulmonary disease and/or otherrespiratory difficulties in a mammal, of

-   -   (a) cetyl myristate, or    -   (b) a mixture of cetyl myristate and cetyl palmitate, or    -   (c) cetyl palmitate.

In another aspect the invention is the use, in the manufacture of oraldosage Its for the treatment of asthma, chronic obstructive pulmonarydisease and/or other respiratory difficulties or prophylaxis of at leastthe symptoms of asthma, chronic obstructive pulmonary disease and/orother respiratory difficulties in a mammal, or

-   -   (i) cetyl myristate and    -   (ii) cetyl palmitate.

The mixture can use cetyl myristate available from a commercial sourcesuch as EHP Products Inc., PO Box 20727, Mt Pleasant S.C. 29465 or atAmerex Corporation, 770 Sycamore Avenue Suite J148 Vista, Calif. 92083.

The mixture can use cetyl palmitate derived from a source such as, forexample, Quimica Croda, S A de C. V, Circuito Médicos No.47. Apdo.Postal 71-A Cd. Satélite, 53100 Naucalpan, Edo. de México, México oronline at wvw.butterburandsage.com.

Most ideally however the mixture is synthetised from starting materialsutilizing the procedures as disclosed in New Zealand PatentSpecification No. 332959 which involves reacting both myristic acid andpalmitic acid with a cetyl alcohol At an elevated temperature in thepresence of at least one acid catalyst and at least one aromatichydrocarbon. The aromatic hydrocarbon fraction then contains the cetylmyristate and cetyl palmitate from whence it can be crystallised.

The full content of NZ 332959 is here incorporated by way of reference.

This crystallised form can then be ground up, dissolved and mixed with asuitable general pharmacy liquid to be administered to a person. Thecrystals are usually dissolved in hot water before adding to thepharmacy liquid which is usually a sugar syrup available from mostpharmaceutical companies. The liquid is made up to a concentration of70% w/v.

Alternatively the crystals may be ground up into a powder and combinedwith magnesium oxide, silicon oxide and fine di-calcium phosphate. Thispowder can then be transferred into capsules for oral ingestion into thebody. The capsules used are VEGICAP™ that are non-gelatin containing.

The mode of administration is preferably oral. The dosage unit can beeither a swallowable capsule or some alternative (preferably having theactive ingredient(s) as a wax-like solid or can be an orally consumableliquid composition (eg; made up with a general pharmacy type carriersuch as methyl cellulose)).

Other modes of administration can include transdermal, sublingual,parenteral, and suppository delivery.

The oral administration for the treatment of asthma, chronic obstructivepulmonary disease and/or other respiratory difficulties can be inaddition to any other medicament administered for such ailment whetheradministered orally, topically, parenterally, sublingually, etc.

In practice the prevent invention will involve ideally oral selfadministration of effective quantities of cetyl myristate alone or morepreferably as a mixture of both cetyl myristate and cetyl palmitate.

Preferably in any such mixture the cetyl myristate comprises at leastabout half of the mixture or the serial application on a weight toweight basis. It is envisaged that daily doses will vary depending onpatient needs and may rage from 1 to 20 capsules per day. A capsuleideally contains between 5 to 370 mg of the mixture or cetyl myristate.

Trials with a variety of patients reliant upon dosage forms of cetylmyristate alone have shown favourable responses insofar as relief fromthe symptoms of asthma, chronic obstructive pulmonary disease and/orother respiratory difficulties is concerned. It has been found howeverthat enhanced benefits occur where there is at least a small proportionof cetyl palmitate in addition to the cetyl myristate and it is to theuse of one such ratio of these active ingredients that the followingtrial examples relate.

Examples of use follows. Each briefly describes tic patient's conditionbefore and after the stated treatment using dosage forms (ie; “of theinvention”) each having about 350 mg of the mixture of cetyl myristateand cetyl palmitate. That mixture comprises by weight 95% cetylmyristate and 5% cetyl palmitate by weight manufactured by the processas disclosed in NZ Patent Specification No. 332959. In addition addedexcipients were present in the admixture and then encapsulated in thenon gelatin two part capsule case.

Accordingly the present invention consists in a method of treatment forasthma, chronic obstructive pulmonary disease and/or other respiratorydifficulties (or other mammal) which comprises administering or havingself administered to such human or other mammal an effective amount ofeither

-   -   (a) cetyl myristate, or    -   (b) cetyl myristate and cetyl palmitate.

Preferably said administration and/or self administration is byingestion.

Preferably the administration and/or self administration is with amixture of cetyl myristate in conjunction with cetyl palmitate where thecetyl myristate comprises, from 50 to 98% w/w.

In a further aspect the present invention consists in the use of aneffective amount of either

-   -   (a) cetyl myristate, or    -   (b) cetyl myristate and cetyl palmitate        in the manufacture of a dosage unit or pharmaceutical        composition for oral ingestion useful in the treatment of        asthma, chronic obstructive pulmonary disease and/or other        respiratory difficulties.

Preferably said use involves the use of an appropriate encompassingcapsule.

The present invention also consists in a pharmaceutical composition fortreating asthma, chronic obstructive pulmonary disease and/or otherrespiratory difficulties which comprises an effective amount of cetylmyristate with an effective amount of cetyl palmitate.

In a further aspect the present invention consists in a dosage uniteffective in the treatment of asthma, chronic obstructive pulmonarydisease and/or other respiratory difficulties said dosage unitcomprising either

-   -   (a) cetyl myristate in an appropriate orally deliverable dosage        unit, or    -   (b) a mixture of cetyl myristate and cetyl palmitate in a        suitable orally administrable dosage unit.

Preferably said cetyl myristate in any such mixture comprises from 50 to98% w/w of the mixture.

In still a further aspect the present invention consists in a dosageunit In the form of a capsule for treating asthma, chronic obstructivepulmonary disease and/or other respiratory difficulties capable ofreleasing its content once ingested orally, said contents being amixture of cetyl myristate with cetyl palmitate.

Preferably said cetyl myristate comprises from 50 to 98% w/w of themixture

Preferably said contents is a wax like powder.

Preferably said powder is placed inside a capsule eg. a gelatine capsulewithout an end.

Preferably said capsule may include a pharmaceutically acceptableexcipient.

Preferably said pharmaceutically acceptable excipient is in solid form.

Preferably said pharmaceutically acceptable excipients includes traceelements such as calcium phosphate or magnesium oxide.

In still a further aspect the present invention consists in a liquid orother soluble form which comprises, a mixture of

-   -   (a) cetyl myristate, or    -   (b) a mixture of cetyl myristate and cetyl palmitate where the        mixture maybe carried in a suitable liquid for oral ingestion        useful in the treatment of asthma, chronic obstructive pulmonary        disease and/or other respiratory difficulties.

Preferably said suitable liquid is a general pharmacy liquid.

Preferably said cetyl myristate and any such mixture comprises from50-98% w/w of the mixture.

This invention may also be said broadly to consist in the parts,elements and features referred to or indicated in the specification ofthe application, individually or collectively, and any or allcombinations of any two or more of said parts, elements or features, andwhere specific integers are mentioned herein which have knownequivalents in the art to which this invention relates, such knownequivalents are deemed to be incorporated herein as if individually setforth.

The invention consists in the foregoing and also envisages constructionsof which the following gives example.

TRIAL EXAMPLES

Patient 1 is Male and is 50 Years of Age.

Patient 1 has suffered from chronic obstructive pulmonary disease forthe past 2 years. Patient 1 was previously on prescribed medicationincluding 1 canister of VENTOLIN™ as required, at a rate of one canisterper week (each canister has at least 200 doses). Patient 1 was alsoprescribed FLIXOTIDE™ at a rate of 200 micrograms twice daily andBAMBEC™ at a rate of 10 milligrams per day.

At the first appointment Patient 1 was provided with capsules of adosage unit as described in invention for a dosage regime of 4 capsules,three times daily.

Within 2 weeks Patient 1's health began to improve with breathingbecoming easier.

Patient 1 is now on a dosage regime of 2 capsules, twice daily and nowonly uses one canister of VENTOLIN™ every two weeks and the amount ofFLIXOTIDE™ has also significantly reduced.

Patient 2 is Male and is 74 Years of Age.

Patient 2 suffers chronic obstructive pulmonary disease and has been anasthmatic for many years.

Patient 2 was previously on prescribed medication including FLIXOTIDE™ 1putt twice daily, NUELIN™ tablets 1 350 mgs tablet twice daily, INTAL™dose twice daily and RESPOLIN™.

At the first appointment Patient 2 was provided with capsules of adosage unit as described in this invention for a dosage regime of fourcapsules, four times daily.

Patient 2 after 2 months, no longer needed to use RESPOLIN™ and hisother prescribed medications were significantly reduced. Patient 2 isnow on maintenance dose of 2 capsules twice daily.

Patient 3 is Male and is 59 Years of Age.

Patient 3 is an asthmatic. His previously prescribed medication included1 atomiser canister of RESPOLIN™, where he was taking 8 puffs daily.This canister lasted one mouth.

At the first appointment Patient 3 was provided with capsules of adosage unit as described in this invention for a dosage regime of 4capsules three times daily which was also taken in conjunction with 1capsule (125 micrograms) of FLIXOTIDE™ daily.

After taking the present invention for 2 months Patient 3 no longerneeded RESPOLIN™ and now continues to do well on a maintenance dose of 2capsules daily.

Patient 4 is Female and is 25 Years of Age.

Patient 4 suffers chronic asthma, is unable to exercise and was oftenhospitalised for asthma related incidences.

Her previous prescribed medication included 1 canister of VENTOLIN™being used at a rate of 1-2 puffs every 4 hours, this canister wouldlast a week, FLIXOTIDE™ and numerous courses of oral prednisone.

At the first appointment Patient 4 was provided with capsules of adosage unit as described in this invention for a dosage regime of 4capsules, four time daily.

Patient 4 has been on this dosage rate for the past 12 months and is nowusing only one VENTOLIN™ canister that lasts 3-4 months

Patient 4 is now able to exercise and living a normal life.

Patient 4 is now on a maintenance dose of 3 capsules twice daily.

Patient 5 is Female and is 82 Years of Age.

Patient 5 is asthmatic and suffers from chronic obstructive pulmonarydisease. Her previously prescribed medication included ATROVENT FORTE™at a rate of 4 puffs daily or as required. NUELIN SR™ at a rate of 250milligrams twice daily, and FLIXOTIDE™ of 550 micrograms twice daily.Patient 5 has taken this medication for a number of years.

At the time of treatment her Peak Flow (a measurement of lung capacity)was 106 and she had a very heavy chest.

At the first appointment Patient 5 was provided with capsules of adosage unit as described in this invention for a dosage regime of 4capsules twice daily.

After being on this dosage regime for the past year, her chest has nowcleared and her Peak Flow has now increased to 150. She now visits thedoctor once every few month as opposed to nearly every month for herrespiratory problems.

Patient 5 now has maintained her Peak Flow rate at 150 and has reducedthe amount of NUELIN™ and ATROVENT FORTE™. She continues to do well on amaintenance dose of 3 capsules twice daily.

Patient 6 is Female and is 59 Years of Age.

Patient 6 has suffered asthma since 1986 when she was diagnosed but hasalways had breathing difficulties before this date and believes she wasnot diagnosed for many years. Patient 6 has been hospitalised twice foracute asthma attacks and was on prescribed medication includingVENTOLIN™ at a rate of 3 or 4 puffs daily plus BECOTIDE™ at a rate of 2puffs twice daily.

At her first appointment Patient 6 was provided with capsules of adosage unit as described in this invention for a dosage regime of 4capsules four time daily.

Since taking the invention Patient 6 has not been hospitalised and herVENTOLIN™ intake is now reduced to only 1 or 2 puffs every 2-3 monthsand when she feels a cold or infection developing she will use BECOTIDE™once a day, otherwise she has ceased all other prescribed medication.

This Patient now continues to do well on a maintenance dose of 4capsules twice daily in the morning and evening.

Patient 7 is Female and is 7 Years of Age.

Patient 7 is an asthmatic. She has always had a wheezy cough and wasconstantly sick with Bronchitis. Her prescribed medication includedBECOTIDE™ inhaled steroids and FLIXOTIDE™. At the age of 4 hermedication also included FLIXOTIDE™ at a rate of 1 puff of 25 microgramstwice daily.

At the first appointment Patient 7 was provided with capsules of adosage rate as described in this invention for a dosage regime of 2capsules, three times daily.

Patient 7 has been on Meracol for the past two years and now no longeruses any prescribed medication except in the winter months when hermother thinks that she is starting to get a cold. Her mother will thengive her FLIXOTIDE™.

Patient 7 now continues to do well on a maintenance dose of one capsuletwice daily.

Patient 8 is Male and is 4 Years of Age.

Patient 8 at 4 months of age had been prescribed oral VENTOLIN™ andBECOTIDE JUNIOR™ for his wheezy cough and Bronchitis and FLIXOTIDE™ at 1puff of 25 micrograms twice daily. At the age of 8 months Patient 8 wasnebulised. Patient 8 had constant ear and nose infections.

At the first appointment Patient 8 was provided with capsules of adosage unit as described in this invention for a dosage regime of 1½capsules, three times daily.

After one week the wheeziness stopped. He has now been on this dosagerate for the past 17 months and is no longer taking VENTOLIN™ orFLIXOTIDE™.

Visits to the Doctor for respiratory related illnesses have been zeroover the past year. Whereas before he was visiting the Doctor every 2weeks.

Patient 8 now continues to do well on a maintenance of 1-2 capsulesdaily.

1-24. (canceled).
 25. A method of treatment and/or prophylaxis of atleast the symptoms of asthma, chronic obstructive pulmonary diseaseand/or other respiratory difficulties in a mammal, which comprises orincludes administering or having self administered to such mammaleffective amounts of cetyl myristate and cetyl palmitate.
 26. A methodas claimed in claim 25 wherein said administration is orally of amixture of both cetyl myristate and cetyl palmitate, or serially.
 27. Amethod as claimed in claim 26 wherein said administration is with amixture of cetyl myristate in conjunction with cetyl palmitate where thecetyl myristate comprises from 50 to 98% w/w of the mixture.
 28. Themethod as claimed in claim 27 wherein said administration is by means ofone or more capsules.
 29. A method as claimed in claim 28 wherein bothcetyl myristate and cetyl palmitate and/or an admixture are administeredin the ratio w/w of 95:5 respectively.